Approach

History and physical examination (including slit-lamp ophthalmic examination with pupil dilation) in conjunction with imaging of the aortic root and the ascending, descending, and abdominal aorta (echo, computed tomography [CT], magnetic resonance imaging [MRI]) are usually sufficient for diagnosis.[1]

Use of diagnostic criteria

The diagnosis of Marfan syndrome is clinically based using well-defined criteria, namely the revised Ghent diagnostic criteria.[2][3]​​​ This revised diagnostic criteria put more weight on cardiovascular manifestations of the disorder, compared with previously used criteria, with aortic root aneurysm and ectopia lentis now becoming cardinal features.[2][3]​​

Identification of risk factors

Risk factors include the presence of a family history of Marfan syndrome, or of aortic dissection or aneurysm. There is also a weak association with high paternal age.[4]

Other historical considerations

There may be a family history of myopia, astigmatism, strabismus, amblyopia, premature cataract or other lens abnormalities, glaucoma, retinal detachment, dental extraction or braces for dental crowding, hernias, or spontaneous pneumothorax. Patients may have a history of joint pain or low back ache.[1]

Physical examination

Tall stature, wide arm span, high level of pubic bone, high arched palate, arachnodactyly, positive wrist and thumb sign, pectus excavatum, pectus carinatum, scoliosis, striae (other than from pregnancy/weight change), flat feet, thick spectacles for myopia, hernias, aortic or mitral valve murmur may be present.[2][3]​ Spontaneous pneumothorax or emphysematous bullae may present as dyspnoea.[3] Skeletal abnormality may result in other pulmonary complications also presenting as dyspnoea.​

There may be signs of heart failure due to valve disease or cardiomyopathy.[18]

Complete ophthalmic examination, including fundus examination with pupil dilation, is recommended in all patients. There may be signs of lens subluxation or dislocation, cataract, glaucoma, or retinal detachment.[3]

It is possible that the patient may present with signs and symptoms of acute aortic dissection or rupture. This presentation is covered in the complications section.[Figure caption and citation for the preceding image starts]: Positive thumb signFrom the collection of LG Svensson, E Mendrinos, C Pournaras [Citation ends].com.bmj.content.model.Caption@2fde7a8f

Initial investigations

Echocardiography is used initially for aortic root imaging and if not clearly determined CT or MRI may be used.[3][19]​​​

Subsequent investigations

Genetic screening for mutations in the fibrillin-1 (FBN1) gene can confirm the diagnosis if in doubt.[3] In the absence of lens dislocation, genetic testing should be considered to exclude the possibility of Loeys-Dietz syndrome.[19]​ Once detected, the mutation can be used to screen other relatives, and used for antenatal diagnosis and pre-implantation genetic diagnosis. This test is more specific than MRI for dural ectasia, which can also be found in Ehlers-Danlos syndrome.

Abdominal ultrasound, CT, and MRI are used for visualisation of the descending aorta.[19]

Chest x-ray may be performed to exclude the presence of a pneumothorax and may reveal emphysematous bullae.

Lower spine CT scan or MRI can be performed to exclude dural ectasia, where upright imaging may be preferred.[3] This is a widening of the dural membrane surrounding the spinal cord and is a recognised complication of Marfan syndrome. MRI is particularly useful for follow-up investigations to avoid accumulative radiation, assessing aortic size and extent of any dural ectasia.

Plasma homocysteine levels help in unclear cases to differentiate homocystinuria.

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